Neuropathy and inflammation in diabetic bone marrow

Abstract

Summary Diabetes impairs the bone marrow (BM) architecture and function as well as the mobilization of immature cells into the bloodstream and number of potential regenerative cells. Circadian regulation of bone immature cell migration is regulated by β‐adrenergic receptors, which are expressed on haematopoietic stem cells, mesenchymal stem cells, and osteoblasts in the BM. Diabetes is associated with a substantially lower number of sympathetic nerve terminal endings in the BM; thus, diabetic neuropathy plays a critical role in BM dysfunction. Treatment with mesenchymal stem cells, BM mononuclear cells, haematopoietic stem cells, and stromal cells ameliorates the dysfunction of diabetic neuropathy, which occurs, in part, through secreted neurotrophic factors, growth factors, adipokines, and polarizing macrophage M2 cells and inhibiting inflammation. Inflammation may be a therapeutic target for BM stem cells to improve diabetic neuropathy. Given that angiogenic and neurotrophic effects are two major barriers to effective diabetic neuropathy therapy, targeting BM stem cells may provide a novel approach to develop these types of treatments.

Hematopoietic stem cells can differentiate into pericytes and myofibroblast in wound healing, not bone Mesenchymal stem cells

“…It con rmed that HSCs play an important role in wound healing again. Previous studies have found that the number of HSCs in the peripheral blood of diabetic patients and mice is reduced and the differentiation potential is impaired [25]. Diabetic patients and diabetic animals often have di culties in wound healing [26].…”

Neuropeptides, Inflammation, Biofilms, and diabetic Foot Ulcers

“…Studies have shown that topical application of SP accelerates the healing of cutaneous wounds by upregulating vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-β1), endothelial nitric oxide synthase (eNOS), and hypoxia-inducible factor 1-alpha (HIF-1a), as well as by stimulating fibroblast prolifera- tion and collagen deposition [17,18]. Diabetes is associated with bone marrow microenvironmental deficiencies and damaged mobilization of bone marrow stem cells (BMCs) [19][20][21]. Studies have shown that SP promotes diabetic wound healing by restoring the cellular activity of BMCs and enhances endothelial progenitor cell (EPC) mobilization [22,23].…”

“…SP promotes neovascularization through the recovery of blood flow and formation of an elaborate vascular network in ischemic wounds and shows anti-inflammatory effects by suppressing inflammation-mediated spleen enlargement and reducing tumor necrosis factor-alpha in ischemic mice [16]. Studies have shown that topical application of SP accelerates the healing of cutaneous wounds by upregulating vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-β1), endothelial nitric oxide synthase (eNOS), and hypoxia-inducible factor 1-alpha (HIF-1a), as well as by stimulating fibroblast proliferation and collagen deposition [17,18] bilization of bone marrow stem cells (BMCs) [19][20][21]. Studies have shown that SP promotes diabetic wound healing by restoring the cellular activity of BMCs and enhances endothelial progenitor cell (EPC) mobilization [22,23].…”

Bone marrow as a target and accomplice of vascular complications in diabetes

“…We concluded that, in patients with advanced diabetic complications, microangiopathy and sensory neuropathy could cooperate in jeopardizing HSPCs fate and function within the BM before they are liberated into the circulation. A recent review article has summarized the knowledge on neuropathy and inflammation in diabetic bone marrow …”